Pentamidine, nebulized

The patient may be required to receive aerosol pentamidine at home. Before discharge, the nurse checks to make sure that arrangements have been made to deliver the specialized equipment and supplies, such as a Respirgard II nebulizer and diluent, to the home. The nurse also instructs the patient and caregiver on how to administer the drug ... 

When pentamidine is prescribed for aerosol use at home, the nurse reviews the use of the special nebulizer, as well as directions for cleaning and maintaining the nebulizer equipment (see Home Care Checklist Administering Pentamidine at Home). 

Patients suffering from cystic fibrosis often use various aerosolized drugs. To reduce the viscosity of the mucus in the airways, recombinant human deoxyribonuclease is used. This enzyme is the first recombinant protein that has been developed for specific delivery to the lungs via the airways. It has a local action on the mucus in the airways and its absorption is minimal. Another drug that decreases the viscosity of the mucus is acetylcysteine. Aerosolized antibiotics are a further group of therapeutics that is widely used by cystic fibrosis patients. Solutions of antibiotics like tobramycin or colistin are used in nebulizers to prevent exacerbation of the disease. Pentamidine has been used for the prophylaxis of Pneumocystis pneumonia in patients infected with HIV virus, while chronic rejection of lung transplants provided a reason to develop an aerosol formulation of cyclosporine A. 

Reconstitution-The contents of 1 vial must be dissolved in 6 mL Sterile Water for Injection, LISP. It is important to use only sterile water saline solution will cause the drug to precipitate. Place the entire reconstituted contents of the vial into the Respirgard II nebulizer reservoir for administration. Do not mix the pentamidine solution with any other drugs. 

Nebulized pentamidine at the dosage of 300 mg every two weeks should be used in patients with a CD4-I- count less than 100 mm if systemic therapy cannot be tolerated. Sulfadoxine/pyrimethamine (Fansidar), one tablet given once or twice a week, is useful in patients in whom compliance is considered to be a problem. However, it has been associated with hepatotoxicity, Stevens-Johnson syndrome and toxic epidermal necrolysis. 

Pentamidine is an aromatic diamidine (Figure 52-3) formulated as an isethionate salt. Pentamidine is only administered parenterally. The drug leaves the circulation rapidly, with an initial half-life of about 6 hours, but it is bound avidly by tissues. Pentamidine thus accumulates and is eliminated very slowly, with a terminal elimination half-life of about 12 days. The drug can be detected in urine 6 or more weeks after treatment. Only trace amounts of pentamidine appear in the central nervous system, so it is not effective against central nervous system African trypanosomiasis. Pentamidine can also be inhaled as a nebulized powder for the prevention of pneumocystosis. Absorption into the systemic circulation after inhalation appears to be minimal. The mechanism of action of pentamidine is unknown. 

There are many commercially available nebulizers with differing mass output rates and aerosol size distributions which will be a function of operating conditions, such as compressed air flow rate. As described above, for maximum efficacy, the drug-loaded droplets need to be less than 5 pm. In the treatment or prophylaxis of P.carinii pneumonia with nebulized pentamidine where the target is the alveolar space it is preferable to use nebulizers capable of generating droplets of less than 2 pm. 

The administration of nebulized pentamidine has an environmental impact handling the nebulizer, cleaning and preparing it for use, and assisting the patient exposes health-care workers to pentamidine (13). Adverse reactions, such as ocular and pulmonary irritation and irritation of exposed skin, have been reported in health care workers (14). 

Figure 6 shows a photograph of three jet nebulizers. Numerous jet nebulizers are being marketed, and, indeed, some concern has been expressed about the nebulizer epidemic [140,141]. The first two nebulizers shown were selected because they are both used to deliver pentamidine to patients suffering from Pneumocystis carinii pneumonia, a secondary infection in AIDS. Of note, ultrasonic nebulizers have also been used for this purpose. Treatment of this particular disease is the most notable example of nebulizer therapy in recent years. Significantly, no other method of pentamidine aerosol generation is currently available. 

Figure 6 Photograph of (A) Aeromist, (B) Respigard II, and (C) Pari LC Star nebulizers, the first two of which are used to deliver pentamidine.

Pentamidine can cause bronchospasm and airway irritation in humans [9]. This appears to be caused by the pentamidine moiety itself, because similar irritation is seen in nonisethionate salts of pentamidine. Because P. carinii habitats the alveolus and because of the potential adverse effects of pentamidine on the airways, pentamidine ideally should be aerosolized in a small particle, between 1 and 2 pm. Studies that make in vitro comparisons of nebulizers cannot be valid unless the particle sizes are identical. The present state of knowledge cannot allow determination of the most effective device because not all the devices have been comparatively tested in humans [10,11]. The optimal particle size for alveolar deposition is between 1 and 3 pm, with 1 pm achieving more peripheral distribution and less airway distribution [12-14]. However, 19% of particles as small as 2 pm still impact in the tracheobronchial regions. The ideal device should have a particle size of 1 -2 pm with a high output. Particles between 0.5 and 1 pm have relatively less alveolar deposition than particles between 1 and 2 pm. Other features, such as reservoirs, flows, and external filters, may also be important [9]. However, any nebulizer with particle sizes, on average, greater than 8 pm would not deliver adequate dmg to the alveoli. 

The FisoNeb and Pulmosonic nebulizers both operate at a frequency of 1.3 MHz that generates a mass median aerodynamic diameter (MMDA) of 4-6 pm [9,10]. The Pulmosonic nebulizer has been reported not to deliver many particles smaller than 2 pm and, therefore, is unsuitable for pentamidine administration [10]. The Portosonic (DeVilbiss) device is a 2.3-MHz ultrasonic nebulizer and may offer the combination of less than 2-pm MMAD and a high output. In any study using ultrasonic nebulizers, the output and particle size of each device need to be periodically sampled, because the frequency of the piezoelectric crystal may alter with age [10]. Any MMADs between 0.5 and 2 pm are available. The Respirgard nebulizer II has one-way valves that control a drug reservoir, allow entrainment of room air in patients whose minute ventilation is... 

All groups used Respirgard II nebulizer for aerosolized pentamidine. 

The second study was a double-blinded comparative trial of secondary prophylaxis comparing 60 mg aerosolized pentamidine given every 2 wk after five weekly loading bases to placebo using a handheld FisoNeb ultrasonic nebulizer with a 5- xm MMAD particle size [36,37], The study was intended to run 6 mo, but it was terminated early, with a mean follow-up of only 3.7 mo. Aerosolized pentamidine significantly reduced the reoccurrence rate of PCP as compared to controls in this study [37,38]. 

Comparisons of the performance of two nebulizers in the delivery of pentamidine and their effectiveness in a community-based clinical trial have been reported [42]. The systems employed were the Respirgard II and the Fisoneb. Both systems provided comparable protection against PCP. The study supported the effectiveness of aerosolized pentamidine as a solid second-line prophylaxis for HIV-infected individuals who are tolerant to trimethoprim/sulfamethoxazole or dapsone. 

O Doherty MJ, Thomas SHL, Page CJ, Blower PJ, Bateman NT, Nunan TO. Disposition of nebulized pentamidine measured using direct radiolabel 123 iodopen-tamidine. Nuc Med Commun 1993 14 8-11. 

Figure 5 Inhaled mass of nebulized pentamidine as a percentage of the nebulizer charge for two commercially available nebulizers (AeroTech II CIS-US, Bedford, MA, and Respirgard II Marquest, Englewood, CO) plotted against time. (From Ref. 9.)...

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